The purpose of these experiments is to characterize the development of the motor innervation of rat skeletal muscles. This system offers an excellent opportunity to explore the hypotheseis that precise neural connections are formed by neurtons initially making a excess number of functional synapses, and gradually, all but the appropriate contacts are electively eliminated. At birth, muscle fibers are polyneuronally innervated by multiple terminal axons converging onto the single endplate of each fiber. Three weeks later, all but one of the inputs per endplate are eliminated and the fibers are unineuronally innvervated. Two mechanisms of axon loss will be investigated by examining neuromuscular junctions with serial section electron microscopy: Motoneurons appear either to slough the excess branches or to retract and completely reabsorb them into the parent axons. Nerve crush, denervation, selective destruction of sensory and sympathetic fibers will be performed initially to establish the morphological characteristics of regenerating (growth cones), degenerating (sloughed), retracting and skeletomotor nerve fibers. Developing muscles will then be examined for the presence of structures. A second morphological basis of functional polyneuronal innervation that has not been adequately evaluated is electrotonic coupling (via gap junctions) of muscle fibers innervated by different motoneurons. The role of gap junctions will be assessed with regular and freeze-fracture electronmicroscopy. Recent ultrastructural studies indicate that motor development differs in slow, fast and mixed muslces. This will be examined further because non-uniform treatment of the muscles was previously employed. The muscle fibers of an adult motor unit are all of the same fiber type and dispersed throughout the muslce in predictable orderly patterns. Achievement of this pattern from the overlapping arrays of connections in developing muscles implies mechanisms that insure perservation of appropriate contacts. To elucidate these mechanisms, single motor unit properties will be studied using the glycogen-depletion method of Kugelberg and Edstrom, histochemical fiber typing, and isometric tension recording.